The Homeostasis of Cartilage Matrix Remodeling and the Regulation of Volume-Sensitive Ion Channel

Abstract

Degenerative joint diseases of the hips and knees are common and are accompanied by severe pain and movement disorders. At the microscopic level, the main characteristics of osteoarthritis are the continuous destruction and degeneration of cartilage, increased cartilage extracellular matrix catabolism, decreased anabolism, increased synovial fluid, and decreased osmotic pressure. Cell volume stability is mainly regulated by ion channels, many of which are expressed in chondrocytes. These ion channels are closely related to pain regulation, volume regulation, the inflammatory response, cell proliferation, apoptosis, and cell differentiation. In this review, we focus on the important role of volume control-related ion channels in cartilage matrix remodeling and summarize current views. In addition, the potential mechanism of the volume-sensitive anion channel LRRC8A in the early occurrence of osteoarthritis is discussed.

Ion channel-mediated mitochondrial volume regulation and its relationship with mitochondrial dynamics

“…Wu et al‘s study [ 111 ] showed that Drp1 knockout can inhibit mitochondrial autophagy in cells and consequently suppress apoptosis of retinal endothelial cells, thus alleviating diabetic retinopathy. Deng et al [ 112 ] suggested that mitochondrial volume homeostasis may be involved in the homeostasis of cartilage matrix metabolism and play an important role in the progression of arthritis.…”

Single‑cell sequencing, genetics, and epigenetics reveal mesenchymal stem cell senescence in osteoarthritis (Review)

“…Cartilage destruction begins when chondrocytes are stimulated by pro-inflammatory cytokines such as IL-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α ( 29 , 30 ). Disruption of cartilage stromal integrity is caused by increased catabolism/apoptosis of chondrocytes in articular cartilage and decreased chondrocyte anabolism ( 31 , 32 ). IL-1β and TNF-α are among the key pro-inflammatory cytokines involved cartilage destruction in OA ( 27 ).…”

“…IL-1β induced enzymes of the MMP family, mainly interstitial collagenase (MMP-1), streptoglobulinase-1 (MMP-3), and collagenase 3 (MMP-13). These enzymes affect the expression of cartilage collagen ( 24 , 36 ), thereby affecting the balance between cartilage matrix synthesis and catabolism, leading to degenerative cartilage diseases such as OA ( 32 ). In addition, IL-1β induces chondrocytes to produce ADAMTS metalloproteinases ( 36 ), which affects aggrecan expression and regulates cartilage metabolism ( 37 ).…”

Apoptosis Regulation in Osteoarthritis and the Influence of Lipid Interactions

“…Lubricin is a surface-active glycoprotein providing boundary lubrication and preventing cell and protein adhesion. This means that chondrocytes rely on a delicate anabolic and katabolic balance to maintain joint homeostasis [3]. Joint autophagy plays an important role in the orderly degradation and recycling of cellular and ECM components within the joint [4,5].…”